Search

Objective To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. Summary background data The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. Methods Patients underwent transcatheter aortic arch repair with a single branch, two stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the two stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid - carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through one year. Survival analysis used the Kaplan-Meier method. Results Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5(17.8%) had combined or other pathologies. At one month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all non-disabling) and combined mortality/stroke rate was 10.7%. One year mortality was 10.7%, without device or aneurysm related death. Two patients (7.1%) reported stroke or transient ischemic attack at one year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were three patients (10.7%) that had device related unplanned reinterventions through one year. Conclusions The NEXUS Aortic Arch Stent Graft System, a novel single branch, two stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent one year safety and performance.

The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.

Participation in the health care and government advocacy arena may represent new and challenging perspectives for the traditional neurosurgeon. However, those with a strong understanding of the laws, rules, regulations, and fiscal allocation process can directly influence the practice of neurosurgery in the United States. We seek to shine light on the black box of how health care laws are passed, the influence and techniques of lobbying, and the role and rules surrounding political action committees. This practical review of health care advocacy is supplemented by a blueprint for engagement in the political arena for the practicing neurosurgeon.

The American Association of Neurological Surgeons/Congress of Neurological Surgeons Washington Committee was formed in 1975 to establish a means for neurosurgery to influence federal health care policy. In response to growing federal health care legislation and regulation, the Washington Committee expanded from its original six members in 1975 to 35 invited liaisons and members by 2020. The Washington Committee, through the Washington Office, expanded political lobbying capacity into numerous important areas of health care policy, including Current Procedural Terminology coding and Medicare reimbursement, Federal Drug Administration (FDA) regulation, healthcare quality oversight, emergency medical services, treatment guidelines, treatment outcome registries, medical liability reform, research funding, and information dissemination. Over 45 yr, the Washington Committee has become an indispensable resource for shaping public policy affecting neurosurgery training, research, and practice.

Objetivo: Avaliar a qualidade da Terapia Nutricional Enteral em unidades de terapia intensiva pediátrica, através da aplicação de indicadores de qualidade. Métodos: Trata-se de um estudo de corte transversal prospectivo, composto por amostra de conveniência com pacientes de ambos os sexos, com idade de 0 até 18 anos incompletos, internados em unidades de terapia intensiva pediátrica e em uso exclusivo de terapia nutricional enteral. Foram aplicados três indicadores de qualidade e realizada a avaliação descritiva dos dados. Resultados: Participaram do estudo 20 pacientes, observou-se que 25% apresentaram pelo menos um episódio de diarreia, 45% estiveram em jejum digestório por mais de 24horas e não houve nenhum registro de obstrução de sonda. Conclusões: Dos resultados encontrados, apenas o indicador obstrução de sonda está dentro da meta proposta. Esse resultado corrobora com outros estudos realizados com adultos, porém são necessários estudos na área pediátrica para confrontar com os dados encontrados.

Aarskog–Scott syndrome is a genetically and clinically heterogeneous rare condition caused by a pathogenic variant in the FGD1 gene. A systematic review was carried out to analyse the prevalence of clinical manifestations found in patients, as well as to evaluate the genotype-phenotype correlation. The results obtained show that clinical findings of the craniofacial, orthopaedic, and genitourinary tract correspond to the highest scores of prevalence. The authors reclassified the primary, secondary, and additional criteria based on their prevalence. Furthermore, it was possible to observe, in accordance with previous reports, that the reported phenotypes do not present a direct relation to the underlying genotypes.

In this article, we propose a temperature-based proportional–integral–derivative (PID) controlling algorithm using highly dense fiber Bragg grating (FBG) arrays for laser ablation (LA) of ex vivo pancreatic tissues. Custom-made highly dense FBG arrays with a spatial resolution of 1.2 mm were fabricated with the femtosecond point-by-point writing technology and optimized for LA applications. In order to obtain proper PID gain values, finite element method-based iterative simulation of different PID gains was performed. Then, the proposed algorithm, with numerically derived PID gains, was experimentally validated. In the experiments, the point temperature was controlled at different distances from the laser fiber tip (6.0, 7.2, 8.4, and 10.8 mm). The obtained results report robust controlling and correlation between controlled distance and the resulting area of ablation. The results of the work encourage further investigation of FBG array application for LA control.

Haploinsufficiency of the methyl-CpG-binding domain protein 5 (MBD5) gene is reported as a cause of an autosomal dominant type of cognitive disability (MRD1) and autism spectrum disorder through large deletions involving multiple genes or point mutations, ultimately leading to haploinsufficiency in both cases. However, relatively few reports have been published on the phenotypical spectrum resulting from point mutations.We report here on a novel heterozygous frameshift variant in the MBD5 gene [c.2579del; p.(Lys860Argfs*11)] in a family in which the typical signs associated with pathogenic variants were expressed with different degrees of severity in the clinical presentation of the carrier individuals.Our findings, adding a novel mutation to the mutational spectrum, further support the relevance of the MBD5 gene as one of the main molecular mechanisms involved in the pathogenesis of intellectual disability and contribute to the characterization of the genotype–phenotype correlations.

OBJECTIVEThe goal of this study was the creation and administration of a survey to assess the depth and breadth of sexual harassment across neurosurgery.METHODSA survey was created to 1) assess perceived attitudes toward systemic issues that might be permissive of sexual harassment; 2) measure the reported prevalence and severity of sexual harassment; and 3) determine the populations at highest risk and those most likely to perpetrate sexual harassment. Demographic information was also included to facilitate further analysis. The SurveyMonkey platform was used, and a request to complete the survey was sent to all Society of Neurological Surgeons and Congress of Neurological Surgeons (CNS) active and resident members as well as CNS transitional, emeritus, and inactive members. Data were analyzed using RStudio version 1.2.5019.RESULTSNearly two-thirds of responders indicated having witnessed sexual harassment in some form (62%, n = 382). Males were overwhelmingly identified as the offenders in allegations of sexual harassment (72%), with individuals in a “superior position” identified as offenders in 86%. Less than one-third of responders addressed the incidents of sexual harassment when they happened (yes 31%, no 62%, unsure 7%). Of those who did report, most felt there was either no impact or a negative one (negative: 34%, no impact: 38%). Almost all (85%) cited barriers to taking action about sexual harassment, including retaliation/retribution (87%), impact on future career (85%), reputation concerns (72%), and associated stress (50%). Female neurosurgeons were statistically more likely than male neurosurgeons to report witnessing or experiencing sexual harassment, as well as assessing it as a problem.CONCLUSIONSThis study demonstrates that neurosurgeons report significant sexual harassment across all ages and practice settings. Sexual harassment impacts both men and women, with more than half personally subjected to this behavior and two-thirds having witnessed it. Male dominance, a hierarchical environment, and a permissive environment remain prevalent within the neurosurgical community. This is not just a historical problem, but it continues today. A change of culture will be required for neurosurgery to shed this mantle, which must include zero tolerance of this behavior, new policies, awareness of unconscious bias, and commitment to best practices to enhance diversity. Above all, it will require that all neurosurgeons and neurosurgical leaders develop an awareness of sexual harassment in the workplace and establish consistent mechanisms to mitigate against its highly deleterious effects in the specialty.

Background Estimate the incidence of herpes zoster (HZ), its complications and healthcare utilization rates in adults (≥ 18-years-old) with a wide range of immunocompromised (IC) conditions compared to IC-free cohort. Method A population-based retrospective study using the Valencia healthcare Integrated Databases (VID) (2009–2014). HZ and IC were defined using ICD-9 codes in primary care (PC) and hospitalization registers. Incidence rates (IR), risk of HZ, HZ-recurrence, HZ-complications and healthcare utilization rates were estimated in the IC-cohort compared to IC-free. Results The study population consisted of 4,382,590 subjects, of which 578,873 were IC (13%). IR (in 1000 persons-year) of HZ overall, in IC and in IC-free cohort was 5.02, 9.15 and 4.65, respectively. IR of HZ increased with age in both cohorts and it was higher for all IC conditions studied, reaching up to twelvefold in subjects with stem cell transplantation. IC subjects had 51% higher risk of developing HZ, 25% higher HZ-recurrence and the risk of HZ-complications was 2.37 times higher than in IC-free. HZ-related healthcare utilization was higher in the IC-cohort than in IC-free (number of hospitalizations 2.93 times greater, hospital stays 12% longer, 66% more HZ-specialist visits, 2% more PC visits, sick leaves 18% longer and 20% higher antiviral dispensation). Conclusions Patients suffering from all the IC conditions studied are at higher risk of developing HZ, HZ-recurrence and post-herpetic complications, which implies a substantial morbidity and a high consumption of resources. These results should be considered for vaccine policy implementation.

Made available in DSpace on 2020-12-12T02:14:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Objective: To assess whether single nucleotide polymorphisms (SNPs) in the IL10, IL1A, IL1B, IL4, TNFA, IL6, OPG, RANK, and RANKL genes, “classically” related with periodontitis, could be associated with susceptibility to T2DM, and also with both diseases concomitantly. Background: There are common pathogenic mechanisms in type 2 diabetes mellitus (T2DM) and periodontitis, but the knowledge of the genetic aspect of this is limited. In patients affected by concomitant T2DM and periodontitis, whose incidence is increasing, there is scarce information regarding the gene-phenotype association, including whether there are genes able to influence both diseases as comorbidities. Methods: Periodontal clinical parameters and biochemical profile (Insulin, Fasting Glycemia, HbA1c, Triglycerides, Total Cholesterol, HDL-cholesterol, and LDL-cholesterol) data were obtained from 894 individuals divided into following three groups: Healthy (H; n = 347), Periodontitis (P; n = 348), and Periodontitis + T2DM (P + T2DM; n = 199). DNA from oral epithelial cells was collected for genotyping. Associations between SNPs and pathologies were tested by multiple logistic regression models, adjusting for age, sex, and smoking habits. We also investigated whether there are sex or smoking effects of each SNP in these phenotypes. Results: The rs1143634-GA (IL1B) SNP showed significantly less likely to develop P + T2DM for all population and mainly for women (adjusted OR = 0.37, 95% CI = 0.16-0.88), while women carrying the rs224320 CT (IL4) were more susceptible to develop P + T2DM (adjusted OR = 1.81, 95% CI = 1.04-3.15). Men carrying the rs1800795-CC (IL6) genotype were less likely to develop T2DM (adjusted OR = 0.12, 95% CI = 0.02-0.70, P =.01). Conclusions: Some SNPs in the IL1B, IL4, and IL6 genes demonstrated sex-influenced association with concomitant periodontitis and T2DM, increasing the evidence of a common genetic component between these diseases and contributing with the understanding of their common pathogenic mechanisms. Department of Diagnosis and Surgery São Paulo State University—UNESP School of Dentistry at Araraquara Department of Morphology Genetics Orthodontics and Pediatric Dentistry São Paulo State University—UNESP School of Dentistry at Araraquara Advanced Research Center in Medicine Union of the Colleges of the Great Lakes (UNILAGO) São José do Rio Preto Department of Surgery and Integrated Clinic São Paulo State University—UNESP School of Dentistry at Araçatuba Department of Periodontology University of North Carolina at Chapel Hill—UNC School of Dentistry Department of Diagnosis and Surgery São Paulo State University—UNESP School of Dentistry at Araraquara Department of Morphology Genetics Orthodontics and Pediatric Dentistry São Paulo State University—UNESP School of Dentistry at Araraquara Department of Surgery and Integrated Clinic São Paulo State University—UNESP School of Dentistry at Araçatuba

Although the long-term results of endovascular aortic repair (EVAR) with low-profile devices in patients with hostile iliac anatomies have been published, there are no reported results specifically for narrow aortic bifurcations (NAB). This study investigated the outcomes of EVAR with the INCRAFT device in NAB (16 mm).This multicenter retrospective study involved five vascular surgery centers. From November 2014 until June 2018, 127 patients were treated with the INCRAFT device. The patient population was divided into two groups based on aortic bifurcation diameter. They were designated as the (1) standard aortic bifurcation (SAB) group (16 mm) and the (2) the NAB group (16 mm). Primary end points were the differences between the two groups in terms of technical success, survival at 30 days, iliac limb patency, and reinterventions.The SAB group included 96 patients and the NAB group included 31 patients. The mean aortic bifurcation diameter was 25.5 mm in the SAB group and 13.2 mm in the NAB group. It is noteworthy that, in the NAB group, 21.8% of patients had aortic bifurcations with focal calcific lesions (less than one-third of the circumferential length of the bifurcation) and 48.3% showed extensive calcifications (two-thirds of the circumferential length of the bifurcation), for 29.9% of the patients in the NAB group the aortic bifurcation had a circumferential highly calcific lesion (complete occlusion of the circumferential length of the bifurcation). Technical success was 98.9% in the SAB group and 96.7% in the NAB group (P = .1). The need for iliac component stenting was not significantly different between the groups (SAB 2.0% vs NAB 3.2%; P = .07). The 1-year survival was 97.9% and 96.7% in the SAB and NAB groups, respectively, with no aneurysm-related mortality. The mean follow-up was 18.4 months and 15.3 months in the SAB and NAB groups, respectively. The iliac primary patency was 98.9 % in the SAB group and 96.8% in the NAB group (P = .088), and the primary assisted patency was 100% in both groups.EVAR with INCRAFT in NABs showed acceptable results. In this multicenter study, the results were comparable in terms of technical success and iliac patency rate between patients with SABs and NABs.

OBJECTIVEThe number of children with complex medical conditions surviving to adulthood is increasing. A planned transition to adult care systems is essential to the health maintenance of these patients. Guidance has been established for the general health care transition (HCT) from adolescence to adulthood. No formal assessment of the performance of pediatric neurosurgeons in HCT has been previously performed. No “best practice” for this process in pediatric neurosurgery currently exists. The authors pursued two goals in this paper: 1) define the current state of HCT in pediatric neurosurgery through a survey of the membership of the American Society of Pediatric Neurosurgeons (ASPN) on current methods of HCT, and 2) develop leadership-endorsed best-practice guidelines for HCT from pediatric to adult neurosurgical health care.METHODSCompletion of the Current Assessment of Health Care Transition Activities survey was requested of 178 North American pediatric neurosurgeons by using a web-based questionnaire to capture HCT practices of the ASPN membership. The authors concurrently conducted a PubMed/MEDLINE–based literature review of HCT for young adults with special health care needs, surgical conditions, and/or neurological conditions for the period from 1990 to 2018. Selected articles were assembled and reviewed by subject matter experts and members of the ASPN Quality, Safety, and Advocacy Committee. Best-practice recommendations were developed and subjected to peer review by external expert groups.RESULTSSeventy-six responses to the survey (43%) were received, and 62 respondents (82%) answered all 12 questions. Scores of 1 (lowest possible score) were recorded by nearly 60% of respondents on transition policy, by almost 70% on transition tracking, by 85% on transition readiness, by at least 40% on transition planning as well as transfer of care, and by 53% on transition completion. Average responses on all core elements were < 2 on the established 4-point scale. Seven best-practice recommendations were developed and endorsed by the ASPN leadership.CONCLUSIONSThe majority of pediatric neurosurgeons have transition practices that are poor, do not meet the needs of patients and families, and should be improved. A structured approach to transition, local engagement with adult neurosurgical providers, and national partnerships between pediatric and adult neurosurgery organizations are suggested to address current gaps in HCT for patients served by pediatric neurosurgeons.

Made available in DSpace on 2020-12-12T02:06:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Type 2 diabetes mellitus (T2DM), dyslipidemia and periodontitis are frequently associated pathologies; however, there are no studies showing the peripheral blood transcript profile of these combined diseases. Here we identified the differentially expressed genes (DEGs) of circulating lymphocytes and monocytes to reveal potential biomarkers that may be used as molecular targets for future diagnosis of each combination of these pathologies (compared to healthy patients) and give insights into the underlying molecular mechanisms of these diseases. Study participants (n = 150) were divided into groups: (H) systemically and periodontal healthy (control group); (P) with periodontitis, but systemically healthy; (DL-P) with dyslipidemia and periodontitis; (T2DMwell-DL-P) well-controlled type 2 diabetes mellitus with dyslipidemia and periodontitis; and (T2DMpoorly-DL-P) poorly-controlled type 2 diabetes mellitus with dyslipidemia and periodontitis. We preprocessed the microarray data using the Robust Multichip Average (RMA) strategy, followed by the RankProd method to identify candidates for DEGs. Furthermore, we performed functional enrichment analysis using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis. DEGs were submitted to pairwise comparisons, and selected DEGs were validated by quantitative polymerase chain reaction. Validated DEGs verified from T2DMpoorly-DL-P versus H were: TGFB1I1, VNN1, HLADRB4 and CXCL8; T2DMwell-DL-P versus H: FN1, BPTF and PDE3B; DL-P versus H: DAB2, CD47 and HLADRB4; P versus H: IGHDL-P, ITGB2 and HLADRB4. In conclusion, we identified that circulating lymphocytes and monocytes of individuals simultaneously affected by T2DM, dyslipidemia and periodontitis, showed an altered molecular profile mainly associated to inflammatory response, immune cell trafficking, and infectious disease pathways. Altogether, these results shed light on novel potential targets for future diagnosis, monitoring or development of targeted therapies for patients sharing these conditions. Department of Diagnosis and Surgery School of Dentistry at Araraquara UNESP- São Paulo State University Department of Morphology Genetics Orthodontics and Pediatric Dentistry School of Dentistry at Araraquara UNESP- São Paulo State University Molecular Genomics and Therapeutics Section Genetics of Development and Disease Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health 10 Center Drive Building 10 Room 9D11 Department of Surgery Uniformed Services University of the Health Sciences and Henry Jackson Foundation for the Advancement of Military Medicine Postgraduate Program in Sciences of the University of Franca Department of Genetics Faculty of Medicine of Ribeirão Preto USP – University of São Paulo Department of Biology Faculty of Philosophy Sciences and Letters of Ribeirão Preto USP –University of São Paulo Department of Medical Genetics and Medicine Genomics University of Campinas – UNICAMP Department of Statistics Institute of Mathematics Statistics and Scientific Computing University of Campinas Department of Periodontology University of North Carolina at Chapel Hill – UNC School of Dentistry Advanced Research Center in Medicine Union of the Colleges of the Great Lakes (UNILAGO) Department of Diagnosis and Surgery School of Dentistry at Araraquara UNESP- São Paulo State University Department of Morphology Genetics Orthodontics and Pediatric Dentistry School of Dentistry at Araraquara UNESP- São Paulo State University

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Background: The significance of neutrophil-to-lymphocyte ratio (NLR) has been explored in different diseases. Few studies addressed its role in patients with multiple sclerosis (MS), with promising results regarding its association with disease activity or disability. Objectives: We aimed at confirming the role of NLR as a marker of neuro-inflammation in a cohort of newly diagnosed MS and clinically isolated syndrome (CIS) patients. Furthermore, we compared the validity of NLR with established markers of neuro-inflammation, such as serum neurofilament light chain (Nfl), CSF microvesicles (CSF-MVs) and CSF IgG indices. Methods: We retrospectively selected, from a prospectively collected cohort of newly diagnosed MS/CIS patients hospitalized for diagnostic work-up, 121 patients who underwent CSF examination, brain MRI and blood cell count within the time of hospitalization and did not receive steroid treatment before sample collection. Patients were grouped according to presence of gadolinium enhancement at brain MRI. Results: No association was found between NLR and disease activity, nor with other clinical measures. Nfl, CSF-MVs, Link and Tourtellotte indices were significantly higher in patients with brain MRI activity. Conclusions: Our negative results do not support the use of NLR as a marker of disease activity and disability in patients with MS.

During the COVID-19 pandemic, concerns raised regarding the use of immunosuppressants in multiple sclerosis, even if current data do not support an increased risk of infection. Although fingolimod can be temporarily suspended during COVID-19, the benefit-risk balance of suspension can be challenging. Till now, no adverse events have been described after the resumption of fingolimod, following a previous discontinuation. We report the occurrence of atrioventricular block following fingolimod restart. Fingolimod acts on sphingosine-1-phosphate-axis, a pathway that is altered with COVID-19 and hypoxic conditions. Herein we discuss how these metabolic changes may have influenced fingolimod pharmacology leading to a cardiac event.

Thermal ablation is an acceptable alternative treatment for primary liver cancer, of which laser ablation (LA) is one of the least invasive approaches, especially for tumors in high-risk locations. Precise control of the LA effect is required to safely destroy the tumor. Although temperature imaging techniques provide an indirect measurement of the thermal damage, a degree of uncertainty remains about the treatment effect. Optical techniques are currently emerging as tools to directly assess tissue thermal damage. Among them, hyperspectral imaging (HSI) has shown promising results in image-guided surgery and in the thermal ablation field. The highly informative data provided by HSI, associated with deep learning, enable the implementation of non-invasive prediction models to be used intraoperatively. Here we show a novel paradigm “peak temperature prediction model” (PTPM), convolutional neural network (CNN)-based, trained with HSI and infrared imaging to predict LA-induced damage in the liver. The PTPM demonstrated an optimal agreement with tissue damage classification providing a consistent threshold (50.6 ± 1.5 °C) for the damage margins with high accuracy (~0.90). The high correlation with the histology score (r = 0.9085) and the comparison with the measured peak temperature confirmed that PTPM preserves temperature information accordingly with the histopathological assessment.

This study aimed to describe the impact of mutuality, anxiety, and depression on quality of life (QoL) in patients with heart failure (HF) using cross-sectional, convenient, and consecutive sampling. A total of 97 patients were recruited. Socio-demographic and clinical variables and self-report measures of anxiety, depression, mutuality, and QoL were collected. The results highlighted the pivotal role of mutuality (specifically the domain of shared values between patients and their caregivers) in determining perceptions of physical health. Conversely, depression was a negative determinant of perceptions of both physical and mental health. Future research is needed to describe in-depth and longitudinally the associations between mutuality and QoL in patients with HF.

Background Several immunisation candidates against RSV are in late-stage clinical trials. To evaluate the benefits of a potential vaccination programme, both economic and health benefits will be needed. Health benefits are usually measured in Health-related Quality of Life (HRQoL) loss using standardised questionnaires. However, there are no RSV-specific questionnaires validated for children under 2 years, in whom most RSV episodes occur. Therefore, HRQoL estimates are taken from literature or inadequate tools. We determined HRQoL loss and direct costs due to an RSV episode in children younger than 2 years and their caregivers during a month of follow up, using a new questionnaire administered online. Methods An observational prospective multicentre surveillance study was conducted in children aged younger than two years. Children were recruited from 8 primary care centres and 1 hospital in the Valencia region and Catalonia (Spain). RSV-positive cases were obtained by immunochromatographic test. HRQoL was assessed using a new ad-hoc 38 item-questionnaire developed. Parents of infected children completed 4 questionnaires at four timepoints (day 0, 7, 14 and 30) after diagnosis. Results 117 children were enrolled in the study and 86 (73.5%) were RSV + . Median (interquartile range; IQR) scores were 0.52 (0.42–0.68), 0.65 (0.49–0.79), 0.82 (0.68–0.97) and 0.94 (0.81–1), for days 0, 7, 14 and 30, respectively. Compared to total recovery (Q30), HRQoL loss was 37.5%, 31.5% and 8.9% on days 0, 7 and 14 since diagnosis of the disease. The total median cost per patient (including treatments) was €598.8 (IQR: 359.63–2425.85). Conclusions RSV had almost 40% impact on HRQoL during the first week since onset of symptoms and the median cost per episode and patient was about €600. These results represent a substantial input for health-economic evaluations of future RSV-related interventions such as vaccination.

Introduction: Nursing care in the hospital environment can have an emotional impact on children and families, but humanized care has made this process less traumatic. Objective: To verify if the physiotherapist's care with the children hospitalized in a public hospital occurs in a humanized way from the perspective of the relatives. Methods: This is an observational, descriptive and quantitative study. The population was composed of 20 relatives of children under 12 years of age, hospitalized at least 24 hours, who performed at least three physiotherapy sessions. As an instrument, a questionnaire elaborated by Lopes (2009) was used, adapted by the researchers. Results: The majority of the children were male (55%), mean age 03-24 months (55%), with a predominance of pneumonia (25%). The female gender (95%) was the prevalence of family members, mothers (90%), single women (40%), with ages ranging from 18 to 29 years (50%). Cardiorespiratory Measurement and guidelines (16%) were the most used physiotherapeutic procedures. The care of the physiotherapist was predominant (100%) and the use of playful care was (75%) negative. Conclusion: it was observed that the care of the physiotherapist with hospitalized children occurs in a humanized way, but leaves gaps regarding the use of playfulness.

Background: Demands for health services have been growing sharply. Consequently, the costs of the institutions for their operational maintenance and investments also increase. The challenge of hospital management is to achieve standards of quality and safety for patients, increasing their productivity and minimizing costs. Lean Six Sigma is a well-structured methodology that aims to eliminate waste and activities that do not add value, focused on reducing process variation, eliminating the causes of the defect, and improving performance. As a result, cost reduction, higher quality, and customer satisfaction are observed. Objectives: To define Lean Six Sigma methodology and search references in the literature on its use in Health and specifically in Anesthesiology. Content: How often the waste of medicines, materials and time (rework), as well as the errors that happen in the day-to-day of the anesthesiologist are reported. Anesthesiologists must know the impact of their professional practice, with the purpose of making more appropriate choices, thus reducing the damage to the environment, improving overall health, and reducing costs with health care. The use of the Lean Six Sigma methodology is suggested to make the anesthesia field more sustainable, improving the processes without prejudice to the patient. Conclusion: Lean Six Sigma methodology is a new business management strategy in the health area. It is perfectly inserted in the current context of quality and safety to the patient; therefore, relevant in the practice of anesthesiology. Resumo: Justificativa: As demandas por serviços de saúde têm crescido de forma acentuada. Consequentemente, crescem também os custos das instituições para sua manutenção operacional e investimentos. O desafio da gestão hospitalar é conseguir conquistar padrões de qualidade e segurança para o paciente, aumentar sua produtividade e minimizar os custos. Lean Seis Sigma é uma metodologia bem estruturada que visa a eliminar os desperdícios e atividades que não agregam valor, focada na redução da variação nos processos, elimina as causas do defeito, melhora o desempenho. Como resultado, observa-se redução de custo, maior qualidade e satisfação do consumidor. Objetivos: Definir metodologia Lean Seis Sigma e buscar na literatura referências do uso da metodologia em saúde e especificamente na anestesiologia. Conteúdo: Descreve-se como são frequentes os desperdícios de medicamentos, materiais e tempo (retrabalho), bem como os erros que acontecem no dia a dia do anestesiologista. O anestesiologista deve conhecer o impacto de sua prática profissional, com o objetivo de fazer escolhas mais apropriadas e reduzir assim o dano ao ambiente, melhorar a saúde global e reduzir os custos com assistência à saúde. Sugere-se o uso da metodologia Lean Seis Sigma para tornar a anestesia mais sustentável, com melhoria dos processos, sem prejuízo ao paciente. Conclusão: A metodologia Lean Seis Sigma é uma estratégia de gerenciamento de negócio de fato nova na área da saúde. Insere-se perfeitamente no contexto atual de qualidade e segurança ao paciente, relevante, portanto, na prática da anestesiologia. Keywords: Lean Six Sigma, Management, Anesthesiology, Operating room, Palavras-chave: Lean Seis Sigma, Gestão, Anestesiologia, Centro cirúrgico

A 66-year-old man arrived at our emergency department 3 years after an endovascular aneurysm sealing procedure performed at another center. Computed tomography angiography showed distal migration of a Nellix endoprosthesis (Endologix, Irvine, Calif) and a posterior contained rupture. The left kidney was excluded by an occluded iliac-left renal bypass, which was performed at the time of the Nellix implantation because of unintended coverage. A t-Branch (Cook Medical, Bloomington, Ind) was implanted in an emergency, but the delivery caused disruption of the Nellix limb, requiring relining. Target vessels were bridged with VBX stents (W. L. Gore & Associates, Flagstaff, Ariz). The postoperative course was uneventful except for renal function impairment that was restored 2 weeks later. Keywords: BEVAR, Nellix, EVAS, t-Branch, Type IA endoleak

For the past several decades, medical malpractice claims in the state of Louisiana have been screened by a pretrial medical review panel (MRP). Composed of 3 physicians and 1 attorney, these panels are a method of filtering nonmeritorious lawsuits while expediting creditable claims. Currently, 14 jurisdictions in the United States require medical liability/malpractice cases be heard by an MRP or screening panel prior to trial. In this article, we review the MRP process in Louisiana and compare it to those in other states. Data are presented for the past 10 yr of malpractice claims in Louisiana with an emphasis on the neurosurgery specialty. Finally, the benefits and challenges of pretrial screening panels are discussed.

Antecedentes: Los catéteres doble j, son herramientas ampliamente utilizadas en urología, sin embargo, al tratarse de un cuerpo extraño en el tracto urinario estos presentan efectos adversos tras su aplicación hasta en el 30 % de los casos. Estos síntomas son atribuidos a la irritación local del espiral del catéter en la vejiga o si se encuentra en el cáliz renal. Numerosos estudios demuestran que la tamsulosina y algunos anticolinérgicos disminuyen los síntomas relacionados a catéteres ureterales. Materiales y métodos: Se realizó un estudio prospectivo observacional, aleatorizado y comparativo. La distribución se hizo de forma aleatoria de casos consecutivos 1 a 1. Los pacientes fueron sometidos a tratamiento endourológico, con ureteroscopia semirrígida y/o flexible, así como litotricia neumática y/o láser. Se obtuvieron dos grupos, incluyendo un total de 77 pacientes, 39 pacientes asignados al grupo 1 que recibieron tamsulosina 0.4 mg por vía oral cada 24 horas durante un mes posterior a la cirugía y 38 pacientes asignados al grupo 2, que recibieron 20 mg de butilhioscina por vía oral cada 8 horas por un mes posterior a la cirugía. La evaluación se realizó en el consultorio de urología, se aplicó el cuestionario validado Ureteric Stent Symptom Questionnaire (ussq), a la semana 1, 2, y 4 posterior a la inserción del catéter doble J. Resultados: Ambos tratamientos disminuyeron los síntomas irritativos y el dolor desde la segunda semana, presentando significancia estadística en la semana 4 respecto a la basal obtenida en la semana 1 (p

Alcohol consumption, pregestational overweight and other associated-factors in users of São Francisco Valley’s public Health system, Northeastern Brazil

Background Nurses are disproportionately prone to experience incidents of violent victimization. Despite the vast literature on violence in healthcare settings, few studies have identified effective violence prevention interventions. Aim The aim of the study was to explore the experiences of nurses regarding the implementation of technology-based violence prevention interventions. Methods Qualitative data were collected through semi-structured focus groups and interviews with 11 nurses at Humber River Hospital. Interviews were audiotaped, transcribed and subjected to a content analysis to identify core themes from the data. Results Three themes were identified: reassurance of safety, an increase in proactive measures and limitations of technology. Nurses held positive perceptions of the impact of technology-based interventions on violent incidents. The interventions were regarded as effective for the detection of potentially violent patients as well as for providing assistance from security staff when a violent incident occurs or appears imminent. However, nurses also acknowledged that patient-related violence was "unavoidable" and that technology cannot fully prevent violence from occurring. Conclusion The findings from this study support the replication of these interventions in other healthcare facilities. Engaging staff, patients and families in this unique digital and technology-enriched environment has been critical for the successful implementation of the violence prevention electronic flagging system. Patient and family education and communication were essential for addressing concerns related to "labelling."

Gasoline replacement with alternative non-fossil fuels compatible with existing units is widely promoted around the world to reduce the dependency on oil-based products by adopting domestic renewable sources. In this context, the possibility to obtain bio-alcohols from non-edible residues of food and plants is particularly attractive for gasoline replacement in SI (Spark Ignition) engines. Such bio-fuels are characterized by higher laminar flame speed (LFS) and octane rating, resulting in improved thermal efficiency and reduced regulated emissions. Low-carbon alcohols (e.g. ethanol) are disadvantageous as gasoline replacement due to poor energy density and high corrosive action on distribution pipelines, whereas high-carbon ones (e.g. n-butanol) are particularly promising candidates thanks to the physical properties and the energy density closer to those of gasoline. High latent heat of vaporization and low saturation pressure are the most relevant weaknesses of n-butanol related to gasoline replacement in DISI (Direct Injection SI) power units. On equal injection pressure and phasing, the slow evaporation rate of n-butanol leads to poor mixture preparation and larger fuel deposits. In particular, this is emphasized by low charge and wall temperatures during part load operation, reducing combustion efficiency and promoting the formation of pollutant particles. Split injection is a promising strategy to improve charge preparation contemporary reducing fuel deposits and improving mixture homogeneity, mostly for low-evaporating fuels. In the present work different split injection strategies are tested in an optically accessible SI engine fueled with n-butanol and simulated through CFD with the aim of identifying trends and understanding the root causes behind measured behaviors. CFD simulations help in understanding changes in charge stratification using different injection strategies, allowing to explain both combustion behavior and soot formation tendency from the analysis of fuel distribution. Mixture quality in the spark region and the presence of very rich mixture pockets in the combustion chamber are identified as the most critical aspects that should be optimized when changing the injection strategy; this in turn contributes to avoid slow burn rates or excessive soot production during operation with low evaporating fuels such as n-butanol. A strong correlation between diffusive flames and rich mixture pockets is found in terms of both location and intensity, proving the first order role of fuel deposits formation and mixture homogenization on both combustion development and soot formation.

In this article we have sought to identify strategies to facilitate urban mobility planning in Brazilian cities. These plans follow bold guidelines, such as giving priority to active and collective public transport modes. The challenge, therefore, is to overcome the resistance of social agents who are unwilling to make sacrifices for the benefit of the community. Among the methodological procedures, the authors analyze the main challenges facing urban mobility in Brazil, introduce Mancur Olson's ideas on the logic behind collective action to transport engineering and evaluate two proposals for an urban mobility pact: that of the then President Dilma Rousseff and that of the Ipea. The result of this analysis points to the need for an urban mobility pact following “win-win” reasoning. A pact that involves not only the public authorities, but also various private social agents, and according to “win-win” reasoning: they win if they participate and the community wins with their participation.

Objective The Gore Excluder Iliac Branch Endoprosthesis (IBE) was developed to preserve perfusion in the hypogastric artery after endovascular repair of aorto-iliac aneurysms. This study reports the 12 month technical and clinical outcomes of treatment with this device. Methods This study was a physician initiated international multicentre, prospective cohort study. The primary endpoint was primary patency of the hypogastric branch at 12 months. Secondary endpoints included technical and clinical outcomes. Patients with an indication for elective treatment with the Gore Excluder IBE were enrolled between March 2015 and August 2018. Baseline and procedural characteristics, imaging data, physical examinations and questionnaire data (Walking Impairment Questionnaire [WIQ], EuroQol-5-Dimensions [EQ5D], International Index of Erectile Function 5 [IIEF-5]) were collected through 12 month follow up. Results One hundred patients were enrolled of which 97% were male, with a median age of 70.0 years (interquartile range [IQR] 64.5 – 75.5 years). An abdominal aortic aneurysm (AAA) above threshold for treatment was found in 42.7% and in the remaining patients the iliac artery diameter was the indication for treatment. The maximum common iliac artery (CIA) diameter on the Gore Excluder IBE treated side was 35.5 mm (IQR 30.8 – 42.0) mm. Twenty-two patients received a bilateral and seven patients had an isolated IBE. Median procedural time was 151 minutes (IQR 117 – 193 minutes) with a median hospital stay of four days (IQR 3 – 5 days). Primary patency of the IBE at 12 month follow up was 91.3%. Primary patency for patients treated inside and outside the instructions for use were 91.8% and 85.7%, respectively (p = .059). Freedom from secondary interventions was 98% and 97% at 30 days and 12 months, respectively. CIA and AAA diameters decreased significantly through 12 months. IIEF-5 and EQ5D scores remained stable through follow up. Patency of the contralateral internal iliac artery led to better IIEF-5 outcomes. WIQ scores decreased at 30 days and returned to baseline values through 12 months. Conclusion Use of the Gore Excluder IBE for the treatment of aorto-iliac aneurysms shows a satisfactory primary patency through 12 months, with significant decrease of diameters, a low re-intervention rate, and favourable clinical outcomes.

Accurate treatment monitoring and control are essential factors to ensure safe and effective outcomes of thermal ablation therapies. In this work, we report a temperature feedback-controlled laser ablation system based on fiber Bragg grating (FBG) array measurements. A highly spatially resolved array of FBGs spaced at a distance of 0.01 mm was adopted to achieve accurate measurement of high-gradient temperature profiles during laser ablation in biological tissue. The temperature feedback-control based on FBG array measurements and on the subsequent laser current regulation was implemented to maintain stable peak temperature during ablation. The laser current was controlled based on the selection of threshold values, set for the maximum temperature in the laser-irradiated area, i.e., 43 °C, 48 °C, 55 °C, and 60 °C. The feedback-controlled system was validated comparing measured temperature maps during ablation and ablation results on the tissue surface. Finally, results suggest that our feedback system allows controlling the spatial extension of the ablated zone and preserving the maximum tissue temperature within useful ranges for a desired and optimal thermal ablation outcome.

Objectives To assess the effectiveness of the HPV vaccines in preventing genital warts (GW) in women aged 14–23 years and to estimate the incidence of GW in the whole population aged from 14 to 65. Design Population-based retrospective cohort study using real-world data from the Valencia health system Integrated Databases (VID). Study population All subjects aged 14–65 years residing in the Valencia Region during 2009–2017 (n = 4,492,724), including a cohort of 563,240 females aged 14–23 years followed-up for the vaccine effectiveness (VE) estimations. Main outcome measures Incident cases of GW defined as the first activation of GW-related codes (ICD-9-CM 078.11 or ICD-10-CM A63.0) in hospital, primary and specialized care during the study period. Adjusted VE was estimated as (1-Relative Risk (RR)) × 100 by a negative binomial Bayesian model. Results There were 23,049 cases of GW in the overall population and 2,565 in the females’ cohort 14–23 years old. The incidence rate (IR) (in 100,000 persons-year) was 69.1 (95% CI 68.21–69.99) in the population overall, being higher in men (72.73; 95% CI 71.45–74.04). The IR of GW was 104.08 (95% CI 100.79–108.94) in the cohort of young women. The RR of GW increased with age from 14 to 21 years, reaching a plateau from 21 to 23. The VE of a complete schedule was 74% (95% CrI 68–79) for quadrivalent HPV vaccine (HPV4v). No effectiveness was seen with a full vaccination course with the bivalent HPV vaccine (HPV2v) in girls up to 21 years old. GW IR tends to be higher in unvaccinated cohorts covered by HPV4v vaccine than in unvaccinated cohorts not covered by HPV4v vaccine. Conclusions A complete HPV4v vaccination schedule was 74% effective in reducing GW in our population. Our results also suggest an indirect protection to unvaccinated and HPV2v vaccinated girls.

Introdução: A hipertensão arterial na gestação preditor de baixo peso ao nascer. Objetivo: Investigar a associação entre hipertensão arterial materna e o peso ao nascer inferior a 3.000g, entre indivíduos a termo. Método: Estudo tipo caso-controle, realizado em Juazeiro - Bahia e Petrolina – Pernambuco, entre 2009 e 2011. Calculou-se Odds Ratio e intervalos de confiança de 95% na análise de dados. Resultados: Gestantes com hipertensão tiveram 49% de chance a mais de ter filhos com peso inferior a 3.000g, quando comparadas às sem hipertensão arterial. Conclusão: A identificação precoce da hipertensão arterial na gestação evita danos desse agravo, especialmente baixo peso ao nascer.

Objective In recent years, manufacturers have developed new stent grafts with lower profiles to increase the endovascular aneurysm repair applicability. As reported by the current European Society for Vascular Surgery guidelines, long-term evaluation of such low-profile platforms is strongly recommended. This study aims to report outcomes beyond 5 years from a multicenter registry, including a real-world cohort of patients electively treated with low-profile stent grafts. Methods A retrospective data collection of patients who had undergone elective implantation of low-profile endograft ≤16 Fr. (Zenith LP, Ovation, Incraft) was performed in nine centers. The primary endpoint was a long-term primary clinical success. Secondary endpoints were survival rate, freedom from abdominal aortic aneurysm (AAA)-related death, freedom from type I to III endoleak, limb patency, and freedom from all reinterventions. The Kaplan-Meier curves were stratified for investigative devices. A multivariate analysis evaluated predictors of primary clinical success and reintervention rate. Results A total of 619 patients were enrolled (Ovation, n = 373; Incraft, n = 111; and Zenith LP, n = 135), with a mean follow-up of 56.8 ± 22.8 months. The overall primary and the secondary clinical success rate at 8 years was 72.1% and 93.8%, respectively. At 8 years, overall survival was 53.2%, freedom from AAA-related death was 94.4%, freedom from reintervention was 74%, freedom from type I/III endoleak was 86.9%, and limb patency was 90.4%. A significantly worse primary clinical success of the Zenith LP was recorded as dependent on more limb-related events. No differences between platforms were registered in the rate of AAA-related deaths, open conversion, sac enlargement, and type I/III endoleaks (P = .26). Multivariate analysis identified iliac tortuosity (hazard ratio, 2.053) and Zenith LP (hazard ratio, 3.818) as significant independent predictors of clinical failure and reintervention. Conclusion Low-profile stent grafts have acceptable long-term outcomes. Overall survival and AAA-related death were in line with those reported for traditional devices. Long-term surveillance and reintervention, when necessary, remain crucial to guarantee durability.

Background To guide decision-making on immunisation programmes for ageing adults in Europe, one of the aims of the Vaccines and InfecTious diseases in the Ageing popuLation (IMI2-VITAL) project is to assess the burden of disease (BoD) of (potentially) vaccine-preventable diseases ((P)VPD). We aimed to identify the available data sources to calculate the BoD of (P)VPD in participating VITAL countries and to pinpoint data gaps. Based on epidemiological criteria and vaccine availability, we prioritized (P) VPD caused by Extra-intestinal pathogenic Escherichia coli (ExPEC), norovirus, respiratory syncytial virus, Staphylococcus aureus, and pneumococcal pneumonia. Methods We conducted a survey on available data (e.g. incidence, mortality, disability-adjusted life years (DALY), quality-adjusted life years (QALY), sequelae, antimicrobial resistance (AMR), etc.) among national experts from European countries, and carried out five pathogen-specific literature reviews by searching MEDLINE for peer-reviewed publications published between 2009 and 2019. Results Morbidity and mortality data were generally available for all five diseases, while summary BoD estimates were mostly lacking. Available data were not always stratified by age and risk group, which is especially important when calculating BoD for ageing adults. AMR data were available in several countries for S. aureus and ExPEC. Conclusion This study provides an exhaustive overview of the available data sources and data gaps for the estimation of BoD of five (P) VPD in ageing adults in the EU/EAA, which is useful to guide pathogen-specific BoD studies and contribute to calculation of (P)VPDs BoD.

Annual conferences, educational courses, and other meetings draw a diverse community of individuals, yet also create a unique environment without the traditional guard rails. Unlike events held at one's home institution, clear rules and jurisdiction have not been universally established. To promote the open exchange of ideas, as well as an environment conducive to professional growth of all participants, the leading neurosurgical professional organizations joined to delineate the expectations for anyone who participates in sponsored events. The One Neurosurgery Summit Taskforce on Professionalism and Harassment developed a foundational policy that establishes common expectations for behavior and a unified roadmap for the prompt response to untoward events. We hope that publishing this policy will inspire other medical organizations to establish their own meeting and conference policies. More importantly, we wish to bring greater attention to everyone's responsibility for ensuring a safe and respectful space for education, scientific debate, and networking during organized events.

Purpose:To investigate the natural history of Stargardt disease over a multiyear follow-up.Methods:We reviewed medical records of Stargardt disease patients, with clinical diagnosis of Stargardt disease at a single institution, which was also supported by molecular diagnosis. All patients underwent best-corrected visual acuity, fundus photography, optical coherence tomography, and full-field electroretinography.Results:The study cohort consisted of 157 Stargardt disease patients aged 30.4 ± 1.1 years. Longitudinal analysis (mean follow-up: 3 years) showed a significant worsening of best-corrected visual acuity at an average rate of 1.5 Early Treatment Diabetic Retinopathy Study letters/year (P < 0.001), an enlargement of retinal pigment epithelium lesion area by optical coherence tomography at an average linear rate of 0.10 mm2/year (P < 0.001), and a thinning of central macular thickness at a mean rate of-1.42 m/year (P < 0.001). Survival analysis showed that patients with 2 alleles harboring likely-null variants, on average, reached most severe disease stage, i.e., legal blindness, alteration in both dark-adapted and light-adapted electroretinographic responses, and retinal pigment epithelium lesion area larger than 2.5 mm2 significantly earlier than patients with at least one allele harboring a missense variant.Conclusion:The current longitudinal study showed a significant genotype-phenotype correlation characterization, because patients harboring 2 likely-null alleles reach a severe disease stage about 10 years earlier than patients with at least one missense allele. Purpose:To investigate the natural history of Stargardt disease over a multiyear follow-up.Methods:We reviewed medical records of Stargardt disease patients, with clinical diagnosis of Stargardt disease at a single institution, which was also supported by molecular diagnosis. All patients underwent best-corrected visual acuity, fundus photography, optical coherence tomography, and full-field electroretinography.Results:The study cohort consisted of 157 Stargardt disease patients aged 30.4 ± 1.1 years. Longitudinal analysis (mean follow-up: 3 years) showed a significant worsening of best-corrected visual acuity at an average rate of 1.5 Early Treatment Diabetic Retinopathy Study letters/year (P < 0.001), an enlargement of retinal pigment epithelium lesion area by optical coherence tomography at an average linear rate of 0.10 mm2/year (P < 0.001), and a thinning of central macular thickness at a mean rate of-1.42 m/year (P < 0.001). Survival analysis showed that patients with 2 alleles harboring likely-null variants, on average, reached most severe disease stage, i.e., legal blindness, alteration in both dark-adapted and light-adapted electroretinographic responses, and retinal pigment epithelium lesion area larger than 2.5 mm2 significantly earlier than patients with at least one allele harboring a missense variant.Conclusion:The current longitudinal study showed a significant genotype-phenotype correlation characterization, because patients harboring 2 likely-null alleles reach a severe disease stage about 10 years earlier than patients with at least one missense allele.

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals.

Made available in DSpace on 2021-06-25T10:52:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Few studies evaluate interrelationships between periodontitis (P) and Type 2 Diabetes Mellitus (T2DM). The aim of this study is to investigate the genetic susceptibility to periodontitis alone, or concomitant with T2DM (as comorbidities), analyzing single nucleotide polymorphisms (SNPs) in the Interleukin 17 alpha (IL17A) gene, considering the biochemical profile and smoking habits on the subjects’ periodontal status. We investigated 879 individuals divided into: T2DM subjects also affected by severe or moderate periodontitis (T2DM-P, n = 199); non-diabetics with severe or moderate periodontitis (PERIODONTITIS, n = 342); and healthy subjects (HEALTHY, n = 338). Subjects underwent complete periodontal examination, history of smoking habits, glycemic and lipid biochemical evaluation. DNA from buccal cells was utilized to genotype the SNPs rs2275913, rs3819024 and rs10484879. The impact of the subjects’ biochemical profile was analyzed in their periodontal status. Each SNP was analyzed independently, and as haplotypes, by multiple logistic regressions, adjusted for covariates, and also stratifying the groups by age, sex and smoking habits. Independently of the periodontitis degree, poorly-controlled T2DM subjects showed worse glycemic and lipid profile. Multiple logistic regressions demonstrated that smokers and former-smokers carrying the GG genotype of rs3819024 seemed to have higher risk for T2DM-Periodontitis (OR = 6.33; 95% CI = 1.26–31.77, p = 0.02), and mainly for T2DM alone (OR = 5.11; 95% CI = 1.37–19.06, p = 0.01), than never smokers. We found the potential effect of smoking habits in the association of IL17A-rs3819024-GG with diseased phenotypes. Because the observed wide confidence intervals, further studies enrolling larger populations, and SNPs’ functional evaluations are needed to better understand our findings. Department of Diagnosis and Surgery São Paulo State University – UNESP School of Dentistry at Araraquara Department of Morphology and Pediatric Clinics São Paulo State University – UNESP School of Dentistry at Araraquara Advanced Research Center in Medicine Union of the Colleges of the Great Lakes (UNILAGO) Department of Diagnosis and Surgery São Paulo State University – UNESP School of Dentistry at Araçatuba Department of Periodontology University of North Carolina at Chapel Hill – UNC School of Dentistry Department of Diagnosis and Surgery São Paulo State University – UNESP School of Dentistry at Araraquara Department of Morphology and Pediatric Clinics São Paulo State University – UNESP School of Dentistry at Araraquara Department of Diagnosis and Surgery São Paulo State University – UNESP School of Dentistry at Araçatuba FAPESP: 2014/13295-1 FAPESP: 2016/03753-8 FAPESP: 2016/08070-6 FAPESP: 2016/18313-3 FAPESP: 2018/26367-1 CNPq: 304570/2017-6 CNPq: 445336/2014-5

We have developed a novel microfabrication and assembly strategy for the realization of 3D Microelectrode Arrays (3D MEAs) which allows for simultaneous optical and electrical probing of a Nerve-on-a-Chip® construct. Specific microfabrication and assembly process innovations include "edge-wrapped" metal interconnects and custom Digital Light Processing (DLP) 3D printed transition rigs respectively. A Nerve-on-a-Chip® construct consisting of primary rat Dorsal Root Ganglion (DRG) cells are further seeded and grown atop the 3D MEA for 28 Days in vitro (DIV). Herein, we present results of the fabrication technology including AFM profilometry of interconnects, in addition to Impedance Spectroscopy, Root Mean Square (RMS) noise characterization, mechanical stability of the MEAs and long-term culture viability of the integrated tissue chip (Nerve-on-a-Chip® construct on the 3D MEAs) with fluorescence imaging.

Made available in DSpace on 2021-06-25T10:48:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Objective: Genome-wide association studies (GWAS) and literature have identified polymorphisms in the KCNJ11, HNF1A, IRS1, TCF7L2, CDKAL1, CDKN2B, RPSAP52, GPR45 HHEX, IL18, and RUNX2 genes associated with type 2 diabetes mellitus (T2DM) and/or periodontitis (P) in diverse populations, and we sought to evaluate them as genetic risk variants for these diseases in the Brazilian population. Material and methods: Periodontal, glycemic, and lipid data were obtained from 931 individuals divided into: control (n = 334), periodontitis (P; n = 358), and periodontitis associated with T2DM (P + T2DM; n = 239). After genotyping, associations between polymorphisms and pathologies were tested by multiple logistic and linear regressions, adjusting for age, sex, and smoking habits. Results: Considering the studied subjects, the increased risk to develop periodontitis in the periodontitis P + T2DM group was found for HNF1A-rs7957197-TA, CDKAL1-rs7754840-CG, RPSAP52-rs1531343-GC, TCF7L2-rs7903146-TT, and CDKN2B-rs7018475-GG. The association of these genetic variants for TCF7L2 and CDKN2B was confirmed for female, never smokers, and poorly controlled P + T2DM. CDKN2B-rs7018475 was associated with worse glycemic condition and periodontal parameters. Conclusion: These five reported genetic variants were associated in the studied Southeastern Brazilian population as genetic risk variants of periodontitis and T2DM associated to periodontitis as comorbidity. Gene–phenotype associations with sex and smoking habits and the CDKN2B-rs7018475 with the poor glycemic control and more severe periodontal conditions should be further investigated. Clinical relevance: Polymorphisms in the CDKAL1-rs7754840, HNF1A-rs7957197, RPSAP52-rs1531343, TCF7L2-rs7903146, and CDKN2B-rs7018475 might predispose to periodontitis and T2DM associated with periodontitis. These findings may be useful in public health genomics and future advanced clinical practice, since genetic carriage can be measured before disease onset, being of potential great benefit for treatment planning and prognosis in early disease stages. Department of Diagnosis and Surgery São Paulo State University – UNESP School of Dentistry at Araraquara Department of Morphology Genetics Orthodontics and Pediatric Dentistry São Paulo State University – UNESP School of Dentistry at Araraquara Union of the Colleges of the Great Lakes (UNILAGO) Department of Surgery and Integrated Clinic São Paulo State University – UNESP School of Dentistry at Araçatuba Department of Comprehensive Oral Health – Periodontology University of North Carolina at Chapel Hill – UNC School of Dentistry Department of Diagnosis and Surgery São Paulo State University – UNESP School of Dentistry at Araraquara Department of Morphology Genetics Orthodontics and Pediatric Dentistry São Paulo State University – UNESP School of Dentistry at Araraquara Department of Surgery and Integrated Clinic São Paulo State University – UNESP School of Dentistry at Araçatuba

Background. Autoimmune polyglandular syndrome type 1 (APS-1) with or without reversible metaphyseal dysplasia is a rare genetic disorder due to inactivating variants of the autoimmune regulator, AIRE, gene. Clinical variability of APS-1 relates to pleiotropy, and the general dysfunction of self-tolerance to organ-specific antigens and autoimmune reactions towards peripheral tissues caused by the underlying molecular defect. Thus, early recognition of the syndrome is often delayed, mostly in cases with atypical presentation, and the molecular confirm through the genetic analysis of the AIRE gene might be of great benefit. Methods. Our methods were to investigate, with a multigene panel next generation sequencing approach, two clinical cases, both presenting with idiopathic hypoparathyroidism, also comprising the AIRE gene, as well as to comment our findings as part of a more extensive review of literature data. Results. In the first clinical case, two compound heterozygote pathogenic variants of the AIRE gene were identified, thus indicating an autosomal recessive inheritance of the disease. In the second case, only one AIRE gene variant was found and an atypical dominant negative form of APS-1 suggested, later confirmed by further medical ascertainments. Conclusions. APS-1 might present with variable and sometimes monosymptomatic presentations and, if not recognized, might associate with severe complications. In this context, next generation diagnostics focused on a set of genes causative of partially overlapping disorders may allow early diagnosis.

Background Neurosurgical spine specialists receive considerable amounts of industry support that may impact the cost of care. The aim of this study was to evaluate the association between industry payments received by spine surgeons and the total hospital and operating room (OR) costs of an anterior cervical discectomy and fusion (ACDF) procedure among Medicare beneficiaries. Methods All ACDF cases were identified among the Medicare carrier files from January 1, 2013, to December 31, 2014, and matched to the Medicare inpatient baseline file. The total hospital and OR charges were obtained for these cases. Charges were converted to cost using year-specific cost-to-charge ratios. Surgeons were identified among the Open Payments database, which is used to quantify industry support. Analyses were performed to examine the association between industry payments received and ACDF costs. Results Matching resulting in the inclusion of 2209 ACDF claims from 2013–2014. In 2013 and 2014, the mean total cost for an ACDF was $21,798 and $21,008, respectively; mean OR cost was $5878 and $6064, respectively. Mann-Whitney U test demonstrated no significant differences in the mean total or OR cost for an ACDF based on quartile of general industry payment received (P = 0.21 and P = 0.54), and linear regression found no association between industry general payments, research support, or investments on the total hospital cost (P = 0.41, P = 0.13, and P = 0.25, respectively), or OR cost for an ACDF (P = 0.35, P = 0.24, and P = 0.40, respectively). Conclusions This study suggests that spine surgeons performing ACDF surgeries may receive industry support without impacting the cost of care.

Made available in DSpace on 2021-06-25T10:35:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-10-01 Objective It is increasingly common to find patients affected by a combination of type 2 diabetes mellitus (T2DM), dyslipidemia (DLP) and periodontitis (PD), which are chronic inflammatory diseases. More studies able to capture unknown relationships among these diseases will contribute to raise biological and clinical evidence. The aim of this study was to apply association rule mining (ARM) to discover whether there are consistent patterns of clinical features (CFs) and differentially expressed genes (DEGs) relevant to these diseases. We intend to reinforce the evidence of the T2DM-DLP-PD-interplay and demonstrate the ARM ability to provide new insights into multivariate pattern discovery. Methods We utilized 29 clinical glycemic, lipid and periodontal parameters from 143 patients divided into five groups based upon diabetic, dyslipidemic and periodontal conditions (including a healthy-control group). At least 5 patients from each group were selected to assess the transcriptome by microarray. ARM was utilized to assess relevant association rules considering: (i) only CFs; and (ii) CFs+DEGs, such that the identified DEGs, specific to each group of patients, were submitted to gene expression validation by quantitative polymerase chain reaction (qPCR). Results We obtained 78 CF-rules and 161 CF+DEG-rules. Based on their clinical significance, Periodontists and Geneticist experts selected 11 CF-rules, and 5 CF+DEG-rules. From the five DEGs prospected by the rules, four of them were validated by qPCR as significantly different from the control group; and two of them validated the previous microarray findings. Conclusions ARM was a powerful data analysis technique to identify multivariate patterns involving clinical and molecular profiles of patients affected by specific pathological panels. ARM proved to be an effective mining approach to analyze gene expression with the advantage of including patient's CFs. A combination of CFs and DEGs might be employed in modeling the patient's chance to develop complex diseases, such as those studied here. Department of Computer Engineering and Industrial Automation School of Electrical and Computer Engineering University of Campinas (UNICAMP) Department of Morphology Genetics Orthodontics and Pediatric Dentistry School of Dentistry at Araraquara São Paulo State University (UNESP) Department of Medical Genetics and Genomic Medicine University of Campinas (UNICAMP) Department of Diagnosis and Surgery School of Dentistry at Araraquara São Paulo State University (UNESP) Advanced Research Center in Medicine Union of the Colleges of the Great Lakes (UNILAGO) Department of Morphology Genetics Orthodontics and Pediatric Dentistry School of Dentistry at Araraquara São Paulo State University (UNESP) Department of Diagnosis and Surgery School of Dentistry at Araraquara São Paulo State University (UNESP)

Made available in DSpace on 2020-12-12T02:44:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Objective: The aim of this study was to investigate the effects of the long-term alendronate administration on bone healing in defects created in rat calvarias. Materials and methods: Female Wistar rats were randomly distributed into 2 groups: Control (CTL): animals received saline solution once a week; and Alendronate (ALD): rats underwent alendronate treatment (1 mg/kg/weekly). After 120 days from the commencement of treatment, a critical size defect was created in all animals, and 10 animals from each group were sacrificed at 5, 10, 15, 20, 25, 30, 45 and 60-days after the defect creation. On the day of sacrifice, urine and blood samples were collected for determination of the serum levels of bone resorption and formation markers by enzyme linked immunosorbent assay, and the urinary concentration of deoxypyridinoline. Bone mineral density (BMD) in the femurs, descriptive histology, tartrate-resistant acid-phosphatase staining and immunohistochemical analyzes were assessed in the calvaria. Results: Alendronate group showed increased BMD compared to the test group. The concentration of C-terminal telopeptide of type I collagen and deoxypyridinoline decreased significantly, and the concentration of aminoterminal propeptide of procollagen type 1 and osteocalcin were significant lower in the alendronate group. Immunohistochemical analysis showed significant downregulation in the inducible nitric oxide synthase, runt-related transcription factor-2, cathepsin-K and receptor activator of nuclear factor kappa-B ligand expression in the alendronate group. Vascular endothelial growth factor and osteopontin were upregulated in the later periods of alendronate group. Conclusions: Our results suggest that long-term treatment with alendronate did not compromise the repair processing of critical size defects in rat. Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry Department of Health Sciences Implantology Post Graduation Course University Centre of Araraquara – UNIARA Department of Rheumatology School of Medicine University of São Paulo Division of Diagnostic and Surgical Sciences UCLA School of Dentistry Molecular Biology Institute UCLA Advanced Research Center in Medicine Union of the Colleges of the Great Lakes (UNILAGO) Department of Diagnosis and Surgery São Paulo State University (UNESP) School of Dentistry